GHL-Cu is a human blood factor present in trace amounts and thought to be involved in transport and cellular uptake of copper (Pickart, L., Lymphokines 8: 425-446, 1983). Recently, applicants have discovered that GHL-Cu may be used to enhance the wound-healing process and reduce inflammation in injured animals. This discovery is the subject of applicant's U.S. patent application filed Jan. 24, 1985.
The healing of many types of traumatic tissue damage and of aging associated with degenerative conditions is delayed by the excessive production of superoxide anion. After wounding or traumatic tissue injury, cells of the immune system invade the damaged area and secrete copious quantities of toxic oxygen radicals to kill invading bacteria. Often, in cases of impaired healing, the production of superoxide anion further damages tissues and brings in a new influx of immunological cells, thereby creating a vicious circle of damaging events which can greatly delay the sequence within the normal healing process. To obtain proper healing of damaged tissue, it is generally necessary to terminate the production of superoxide anion in the afflicted area.
GHL-Cu possesses significant superoxide dismutase activity, allowing it to detoxify the tissue-damaging superoxide anion. Further, GHL-Cu also inhibits platelet aggregation and the production of the vascoconstrictive and the thrombosis-inducing hormone, thromboxane. GHL-Cu accelerates the healing of wounds in rats, mice and pigs and possesses anti-inflammatory actions in standard rat inflammation models.
However, although valuable, GHL-Cu is susceptible to breakdown by proteolytic enzymes called carboxypeptidases and is poorly soluble in fatty tissues.
Accordingly, it is a primary object of the present invention to improve the resistance of GHL-Cu to breakdown and further to increase the fatty tissue solubility of GHL-Cu, resulting in a more useful form of the molecule.